The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis
Chronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton’s tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow....
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Micromachines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-666X/16/1/95 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587901718757376 |
|---|---|
| author | Anika Alexandrova-Watanabe Emilia Abadjieva Lidia Gartcheva Ariana Langari Miroslava Ivanova Margarita Guenova Tihomir Tiankov Velichka Strijkova Sashka Krumova Svetla Todinova |
| author_facet | Anika Alexandrova-Watanabe Emilia Abadjieva Lidia Gartcheva Ariana Langari Miroslava Ivanova Margarita Guenova Tihomir Tiankov Velichka Strijkova Sashka Krumova Svetla Todinova |
| author_sort | Anika Alexandrova-Watanabe |
| collection | DOAJ |
| description | Chronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton’s tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow. In this study, we applied a microfluidic device and a newly developed Software Image Flow Analysis to assess the extent of RBC aggregation in CLL patients and to elucidate the hemorheological effects of the commonly applied therapeutics Obinutuzumab/Venetoclax and Ibrutinib. The results revealed that, in RBC samples from untreated CLL patients, complex 3D clusters of large RBC aggregates are formed, and their number is significantly increased compared to healthy control samples. The application of the Obinutuzumab/Venetoclax combination did not affect this aspect of RBCs’ rheological behavior. In contrast, targeted therapy with Ibrutinib preserves the aggregation state of CLL RBCs to levels seen in healthy controls, demonstrating that Ibrutinib mitigates the alterations in the rheological properties of RBCs associated with CLL. Our findings highlight the alterations in RBC aggregation in CLL and the impact of different targeted therapies on RBCs’ rheological properties, which is critical for predicting the potential complications and side effects of CLL treatments, particularly concerning blood flow dynamics. |
| format | Article |
| id | doaj-art-10dd1047373544dab3f142d0ee390772 |
| institution | Kabale University |
| issn | 2072-666X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj-art-10dd1047373544dab3f142d0ee3907722025-01-24T13:42:08ZengMDPI AGMicromachines2072-666X2025-01-011619510.3390/mi16010095The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow AnalysisAnika Alexandrova-Watanabe0Emilia Abadjieva1Lidia Gartcheva2Ariana Langari3Miroslava Ivanova4Margarita Guenova5Tihomir Tiankov6Velichka Strijkova7Sashka Krumova8Svetla Todinova9Institute of Mechanics, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 4, 1113 Sofia, BulgariaInstitute of Mechanics, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 4, 1113 Sofia, BulgariaNational Specialized Hospital for Active Treating of Hematological Diseases, Zdrave Str. 2, 1756 Sofia, BulgariaCenter of Competence at Mechatronics and Clean Technologies—MIRACle, “Acad. G. Bontchev” Str. 4, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 21, 1113 Sofia, BulgariaNational Specialized Hospital for Active Treating of Hematological Diseases, Zdrave Str. 2, 1756 Sofia, BulgariaInstitute of Mechanics, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 4, 1113 Sofia, BulgariaInstitute of Optical Materials and Technologies “Acad. Yordan Malinovski”, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 109, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 21, 1113 Sofia, BulgariaCenter of Competence at Mechatronics and Clean Technologies—MIRACle, “Acad. G. Bontchev” Str. 4, 1113 Sofia, BulgariaChronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton’s tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow. In this study, we applied a microfluidic device and a newly developed Software Image Flow Analysis to assess the extent of RBC aggregation in CLL patients and to elucidate the hemorheological effects of the commonly applied therapeutics Obinutuzumab/Venetoclax and Ibrutinib. The results revealed that, in RBC samples from untreated CLL patients, complex 3D clusters of large RBC aggregates are formed, and their number is significantly increased compared to healthy control samples. The application of the Obinutuzumab/Venetoclax combination did not affect this aspect of RBCs’ rheological behavior. In contrast, targeted therapy with Ibrutinib preserves the aggregation state of CLL RBCs to levels seen in healthy controls, demonstrating that Ibrutinib mitigates the alterations in the rheological properties of RBCs associated with CLL. Our findings highlight the alterations in RBC aggregation in CLL and the impact of different targeted therapies on RBCs’ rheological properties, which is critical for predicting the potential complications and side effects of CLL treatments, particularly concerning blood flow dynamics.https://www.mdpi.com/2072-666X/16/1/95chronic lymphocytic leukemiared blood cell aggregationmicrofluidic devicesoftware image flow analysisred blood cell morphologyObinutuzumab |
| spellingShingle | Anika Alexandrova-Watanabe Emilia Abadjieva Lidia Gartcheva Ariana Langari Miroslava Ivanova Margarita Guenova Tihomir Tiankov Velichka Strijkova Sashka Krumova Svetla Todinova The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis Micromachines chronic lymphocytic leukemia red blood cell aggregation microfluidic device software image flow analysis red blood cell morphology Obinutuzumab |
| title | The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis |
| title_full | The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis |
| title_fullStr | The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis |
| title_full_unstemmed | The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis |
| title_short | The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis |
| title_sort | impact of targeted therapies on red blood cell aggregation in patients with chronic lymphocytic leukemia evaluated using software image flow analysis |
| topic | chronic lymphocytic leukemia red blood cell aggregation microfluidic device software image flow analysis red blood cell morphology Obinutuzumab |
| url | https://www.mdpi.com/2072-666X/16/1/95 |
| work_keys_str_mv | AT anikaalexandrovawatanabe theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT emiliaabadjieva theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT lidiagartcheva theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT arianalangari theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT miroslavaivanova theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT margaritaguenova theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT tihomirtiankov theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT velichkastrijkova theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT sashkakrumova theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT svetlatodinova theimpactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT anikaalexandrovawatanabe impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT emiliaabadjieva impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT lidiagartcheva impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT arianalangari impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT miroslavaivanova impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT margaritaguenova impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT tihomirtiankov impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT velichkastrijkova impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT sashkakrumova impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis AT svetlatodinova impactoftargetedtherapiesonredbloodcellaggregationinpatientswithchroniclymphocyticleukemiaevaluatedusingsoftwareimageflowanalysis |